In the development history of vaccines, the vaccine emerged initially was prepared by using attenuated or inactivated pathogenic organisms such as bacteria, viruses, rickettsia and the like. Vaccine formulations obtained in this way have potential biosafety issues in clinical applications, such as causing severe inflammatory and pathogenic viral infections. A purified or recombinant subunit antigen is usually used to replace the complete pathogenic organism in current vaccine formulations, which eliminates the possibility of pathogenic recurrence of the pathogen so that the biosafety of the vaccine in use has been greatly improved. However, protein or polypeptide subunit antigens are susceptible to degradation and are difficult to be uptaken by antigen presenting cells (APCs) compared to intact pathogenic microorganisms. More importantly, the “dangerous signal” post vaccination is deficient due to the lack of pathogen-associated molecular pattern (PAMP), and therefore APCs cannot be effectively activated. These problems make it difficult to obtain a strong immunogenicity when using subunit antigens alone, resulting in an unsatisfactory effect of immune response.
Studies on mechanisms of acquired immunity have shown that although pathogen antigens are important for immune recognition and immune memory, other characteristic components than the antigens in the pathogen also play a significant role in immune response. In the process of interacting with pathogens, the unique morphology, surface biological properties and various secreted biological signals of the pathogen can promote immune-related cells to approach, recognize and phagocytize pathogen components including antigenic components; and in the meanwhile, the PAMP in the pathogen components, upon contacting with or being uptaken by immune-related cells, can effectively activate these cells and induce a high level immune response. The body's immune system can effectively recognize and respond to the pathogens, precisely because they have such a series of important characteristics.
Inspired by this, some researchers have begun to try to develop vaccine formulations with characteristics of pathogens and have achieved some initial success. Take the most successful virosome as an example, it got its name for the imitation of key physiological structure and morphology of virus. Virosome is a class of special liposomes prepared by embedding the functional proteins located on the surface of the virus into the bilayer of liposomes. Envelope proteins of viruses including influenza virus, vesicular stomatitis virus and newcastle disease virus and the like, have been successfully used for the preparation of virosome. Like virus, virosome has a membrane fusion capacity by using the functional viral protein embedded in its lipid layer, and thus can simulate the process of viral infection of the animal body. More importantly, since only a small amount of virus protein with low toxicity is used without involving its genetic substance, virosome obtains a cell invasion ability similar to the virus while avoiding the biosafety issues during the use of live vaccines. To date, two virosome-based vaccines used for human have been marketed in 29 countries. At present, the virosome application is mainly limited to that there are great limitations on antigen loading, and the molecular size and the hydrophobic-hydrophilic properties of antigen are strictly required, and the loading efficiency is also need to be improved.
Although the bionic vaccine formulations represented by virosome are still in the early stages of development, and there are still a variety of deficiencies, the success that has been achieved showed the potential advantages and great development space of the vaccine formulations constructed by imitating pathogens.
Therefore, if a vaccine formulation with similar ability to pathogens in each process including APC uptake, antigen presentation and immune activation can be developed, it is expected to provide an effective solution for the prevention and treatment of many major diseases.